Evidence for internalization of both type 1 angiotensin receptor subtypes (AT1a, AT1b) by a protein kinase C independent mechanism.
We and others have demonstrated the existence of two isoforms or subtypes of the angiotensin type 1 (AT1) receptor, named the AT1a and AT1b receptors. In this study we examined if both types of mouse AT1 receptors are internalized after agonist stimulation and whether protein kinase C (PKC) is involved in this process. To directly visualize the cellular localization of the receptors, an antigenic epitope was engineered onto the amino-terminal of the receptors, and stable cell lines specifically expressing each receptor subtype were isolated. Treatment of these cells with angiotensin II (Ang II) resulted in translocation of surface receptors to intracellular vesicles, together with a reduction in surface binding of Sar1Ile8-Ang II. The agonist-induced internalization of AT1a and AT1b receptors was not inhibited by the PKC inhibitor staurosporine, nor mimicked by the phorbol ester phorbol 12-myristate 13-acetate. Similar results were obtained with cultured rat vascular smooth muscle cells expressing predominantly wild-type AT1a receptors. These results suggest that both AT1a and AT1b receptors are internalized after agonist stimulation by a PKC-independent mechanism.
Sasamura
H
H
Department of Internal Medicine, Keio University, Tokyo, Japan.
Hein
L
L
Saruta
T
T
Pratt
R E
RE
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology; D011485:Protein Binding; D011493:Protein Kinase C / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000819:agonists / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D011493:Protein Kinase C